Beyond Race: A Wake-up Call for Drug Therapy Informed by Genotyping
Authors: Giorgio Sirugo, Ambroise Wonkam
Journal: Annals of Internal Medicine (2022)

EditorialsAugust 2022Beyond Race: A Wake-up Call for Drug Therapy Informed by GenotypingGiorgio Sirugo, MD, PhD and Ambroise Wonkam, MD, PhDGiorgio Sirugo, MD, PhDInstitute of Systems Pharmacology and Translational Therapeutics, and Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PennsylvaniaSearch for more papers by this author and Ambroise Wonkam, MD, PhDMcKusick-Nathans Institute and Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MarylandSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M22-1827 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail People can vary substantially in their response to drugs. Genomic variation accounts for an estimated 20% to 95% of therapeutic effects. The purpose of pharmacogenetics is to understand how genetic variation affects treatment outcomes, with the intent of guiding therapy. Ideally, clinicians should base implementation of treatments “personalized” to patients from diverse populations on specific genetic variants as opposed to proxies such as global ancestry or socially defined race. It is also important to recognize that variation in human genes not involved in drug metabolism can affect therapeutic outcomes.Dickson and colleagues' report on race, genotype, and azathioprine discontinuation is ...References1. Dickson AL, Daniel LL, Jackson E, et al. Race, genotype, and azathioprine discontinuation. A cohort study. Ann Intern Med. 2022;175:1092-9. doi:10.7326/M21-4675 LinkGoogle Scholar2. Dean L. Azathioprine therapy and TPMT and NUDT15 genotype. In: Pratt VM, Scott SA, Pirmohamed M, et al, eds. Medical Genetics Summaries. National Center for Biotechnology Information. 2012. [PMID: 28520349] MedlineGoogle Scholar3. 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The genetic structure and history of Africans and African Americans. Science. 2009;324:1035-44. [PMID: 19407144] doi:10.1126/science.1172257 CrossrefMedlineGoogle Scholar8. Dandara C, Swart M, Mpeta B, et al. Cytochrome P450 pharmacogenetics in African populations: implications for public health. Expert Opin Drug Metab Toxicol. 2014;10:769-85. [PMID: 24588448] doi:10.1517/17425255.2014.894020 CrossrefMedlineGoogle Scholar9. Wu HF, Hristeva N, Chang J, et al. Rosuvastatin pharmacokinetics in Asian and White subjects wild type for both OATP1B1 and BCRP under control and inhibited conditions. J Pharm Sci. 2017;106:2751-7. [PMID: 28385543] doi:10.1016/j.xphs.2017.03.027 CrossrefMedlineGoogle Scholar10. Sirugo G, Tishkoff SA, Williams SM. The quagmire of race, genetic ancestry, and health disparities. J Clin Invest. 2021;131. [PMID: 34060479] doi:10.1172/JCI150255 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Institute of Systems Pharmacology and Translational Therapeutics, and Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PennsylvaniaMcKusick-Nathans Institute and Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MarylandAcknowledgment: The authors thank Scott M. Williams, Philip Tsai, and Jade Hotchkiss for critical reading of the manuscript.Grant Support: Dr. Sirugo was supported by National Institutes of Health (NIH) award U01HG010219. Dr. Wonkam was supported by NIH grants U01HG009716, 5U24HL135600, U01MH127692, and U54HG009790.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-1827.Corresponding Author: Giorgio Sirugo, MD, PhD, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA 19104; e-mail, giorgio.[email protected]upenn.edu.This article was published at Annals.org on 21 June 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoRace, Genotype, and Azathioprine Discontinuation Alyson L. Dickson , Laura L. Daniel , Elise Jackson , Jacy Zanussi , Wenjian Yang , W. Dale Plummer , William D. Dupont , Wei-Qi Wei , Puran Nepal , Adriana M. Hung , Nancy J. Cox , Sara L. Van Driest , QiPing Feng , Jun J. Yang , C. Michael Stein , Jonathan D. Mosley , and Cecilia P. Chung Annals On Call - Understanding Benign Neutropenia Robert M. Centor , Cecilia P. Chung , and Jonathan D. Mosley Metrics August 2022Volume 175, Issue 8Page: 1187-1188KeywordsDrug therapyGeneticsNeutropeniaRacial and ethnic issuesToxicity ePublished: 21 June 2022 Issue Published: August 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...